Notch signal transduction relates to determination of cell fate in youth and adulthood and is a mechanism which is not so changed (Non-Patent Document 1). The Notch signal transduction participates in the determination of cell fate in many tissues. The function of Notch acts on neighboring cells having the same function.
In many cases, it inhibits differentiation toward initial differentiation fate. Instead, it differentiates a cell into second alternative fate or retains the cell in an undifferentiated state. This function is an origin of cell diversity. Other than this role, Notch signal actively promotes differentiation of various types of cells. For example, Notch signal promotes differentiation into astrocytes in a nerve system.
Molecularly, Notch signal was confirmed first in drosophila and then in vertebrates. This depends on a transmembrane receptor encoded by a Notch gene (Non-Patent Documents 1 to 3) and it is activated by a transmembrane ligand (encoded by a gene such as Delta or Jagged). This activation regulates a series of degradation and cleavage of Notch protein and transcription of a fragment which is present in a molecule into a nucleus, which binds to CBF protein. They also act as transcription complexes which activate transcription of HES gene. Since HES inhibits transcription of MASH1 which is a proneuron gene, differentiation of the nerve stem cells into neurocytes is inhibited by activation of Notch in the cells.
By the multifunction thereof, dysfunction of the Notch signal transduction invites various diseases such as tumors, cancers, and neurodegenerative diseases such as Alzheimer's disease (Non-Patent Documents 2 to 3). A cell fate-determining factor acting on Notch signal transduction system becomes a target for novel pharmaceuticals. Since the strategies which have been employed aim at control of Notch function through targeting a factor which exists in downstream of Notch signal system (e.g., suppression of binding of a ligand, inhibition of protein degradation and cleavage of a receptor, suppression of transcription thereof to a nucleus, etc.), they do not suppress expression of Notch.    Non-Patent Document 1: S. Artavanis-Tsakonsa, M. Rand, R. Lake, Notch Signaling: Cell Control and Signal Integration in Development. Science Vol. 284 Page 770-776 (1999)    Non-Patent Document 2: A Zlobin, M. Jang, L. Miele, Toward the rational design of cell fate modifiers: Notch signaling as a target for novel biopharmaceuticals. Current Pharmaceutical Biotechnology July 1(1) Page 86-106 (2000)    Non-Patent Document 3: B. Nickoloff, B. Osborne, L. Miele Notch signaling as a therapeutic target in cancer: a new approach to the development of cell fate modifying agents. Oncogene Vol 22(42) Page 6598-6608 (2003)
The determination of cell fate is an important event in youth as in adulthood. It controls processes such as proliferation, differentiation, and apoptosis of cells. Disorder of such processes is an origin of many clinical conditions.
Therefore, development of a cell fate-determining factor is one of main purposes for the development of pharmaceuticals.